DE1770042A1 - Process for the preparation of alpha, ss-dihalo-gamma-hydroxycrotone lactams - Google Patents

Description

Our reference: OZ 25 467 WB / D Ludwigshafen am Rhein, March 22nd, 1968

Process for the preparation τ / on tkjß-Dihalogen-ST ^ hydroxy-croton-

lac camouflage

This invention relates to a process for the preparation of ^, ß-dihalogen- ^ hydroxy-crotonlactams by reacting muco- ^ halides with primary amines.

It is known, mucobromic acid bromide or mucochloric acid chloride or their pseudo-esters with ammonia to form mucobromide or mucoehloric acid amide implement (American Chemical Journal, Volume 16, page 302 (1894)) · The implementation of the pseudomethyl esters of mueohalogen acids with aniline results in an exchange of the ß-halogen atom the acid by the anilino group (Journal of the American Chemical Society, Vol. 76, p. 1242 (1954)). Furthermore, in Journal of the American Chemical Society, Volume 74 »Page 4094 (1952) the formation of a thiazolidine by the reaction of mucochloric acid described with penicillamine. A work in the reports of the German Chemical Society, Volume 34, page 1010 (1901) contains the rewetting of mucobromic acid and ethylenediamine to connections of the Typu

Am. / COOH Bb COO 3

H-0
I.

> »H-0H ₂ or Cir ^d

\ / 000 V "3 r ^ \ CH = N-CHo.

NH-CH ₂

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The production of # * - Hydroxy- / ^: -aryl - inono-halogencrotone lactams by reacting ^ -aryl - ^, ß-dihalo-csotone lactones with primary amines is also known. (Collection of Czechoslovakia Chemical Communications, Vol. 28, page 3278 (1963)).

The implementation of o-benzoyl-benzoyl-chloride with ethylenediamines gives a phenyl-phthalimidine of the formula

^ ^w . CH ₂ • CH ₂ • NH ₂

HO.

(Journal of Organic Chemistry, Volume 32, pages 2185 ff. (1967); Journal of the American Chemical Society, Volume 73 _t page 4627 (1951) and Volume 66, page 827 (1944)). A reaction of mucohalogen acid halides with amines, in which a lactam ring is formed at the same time and the halogen of the acid halide group is replaced by the hydroxyl group, has not yet been described.

It has now been found that dUß-dihalogen - ^ - hydroxy-crotonlacfcame the general formula

in which R is a hydrogen atom or an aliphatic, cycloali phatic, araliphatic, aromatic or heterocyclic And the individual radicals X are identical or different

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can be and each denote a halogen atom, advantageous obtained when mucolialogic acid halides of the general formula

^τι >

wherein X has the aforementioned meaning with ammonia or primary amines of the general formula

R-MH

III,

in which R has the aforementioned meaning, "at a temperature between -20 and +20 ⁰ C converts.

The implementation can be for the case of using mucochlor acid chloride and cyclohexylamine represented by the following equation:

Eq

J31 + 2

NH

. HCl.

The process according to the invention provides, starting from readily available starting materials, a large number of ^, ß-dihalogeno- ■ Jf-hydroxy-crotonlaetamen in a simple way and in good yield. In view of the prior art it was surprising that Side reactions, e.g. replacement of halogen atoms with amino groups, Cleavage of the mucohalogen acid ring and subsequent reaction of the aldehyde group with the amine, formation of T ^ halocrotonic acid derivatives, do not play an essential role. Also was in the

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same as the above work in Journal of Organic Chemistry the high purity of the end products after the process according to the invention not to be expected, as mucohalogen acid halides are not real acid chlorides such as the mentioned o-benzoyl-benzoyl-chloride represent, but are pseudohalides, where the ^ -chlorine atom just as reactive as the rfv chlorine atoms in cyclic ones Ether is (Houben-Weyl, Methods of Organic Chemistry, Volume 6/2, page 724; Journal of the American Chemical Society. Volume 72, pages 2535 ff (1950)).

Preferred mucohalogen acid halides of the general formula II and correspondingly preferred end products I are those in their Formulas the individual radicals X are identical or different and each represent a chlorine or bromine atom. For example, mucochlor (bromine) acid chlorides can be used or bromides are used as starting materials II.

Preferred primary amines of the general formula II and correspondingly preferred end products I are those in whose formula R is an alkyl, cycloalkyl, aralkyl, aryl radical each having up to 12 carbon atoms or a 5- or 6-membered heterocyclic ring containing 1 or Contain 2 nitrogen atoms and to which, if necessary, a benzene nucleus can also be fused. The starting amine, in stoichiometric amount or in excess, generally in an excess of up to 15 wt. $> On the stöchiometrisehen amount, are reacted with starting material II. For example, the following amines can be used as starting materials III: ammonia, ethylamine, tryptamine, cyclohexyl, cyclo

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looefcyl-, benzylamine, p-anisidine, ρ-nitroaniline, 2-amino-pyrimidine, 2-aminopyrrole, 2-aminopyridine.

The reaction is carried out at a temperature between -20 and +20 ⁰ C, preferably between 0 and 5 ⁰ C, under atmospheric or superatmospheric pressure, continuously or discontinuously. The starting materials are expediently allowed to react in solution and / or suspension. Suitable organic solvents which are inert under the reaction conditions can be hydrocarbons such as ligroin, cyclohexane, toluene; Chlorinated hydrocarbons such as carbon tetrachloride, methylene chloride; ketones such as acetone, cyclohexanone; carboxylic acid esters such as ethyl acetate, butyl acetate; ethers such as diethyl ether, tetrahydrofuran, dioxane; and mixtures of these solvents.

The reaction can be carried out as follows: A mixture of starting materials II and III, optionally together with solvent, is kept at the reaction temperature for 0.5 to 5 hours. The end product is then separated off in the usual way, e.g., by filtering the reaction mixture and concentrating J the filtrate. You can also pour the mixture into water and use the Filter off the crystallized end product or by extraction with a suitable solvent such as methylene chloride.

The compounds which can be prepared by the process of the invention are valuable intermediates for the preparation of insecticides and fungicides. For example, N-substituted dihalomaleimides can be prepared with them by oxidation with fuming nitric acid manufacture which, for example, according to information in US Pat. No. 2,930,694,

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British Patent 8 52 634 and U.S. Patent 2,865,730 have an insecticidal, fungicidal or herbicidal effect. They are also obtained by reaction with reducing agents cyclic imides which, according to information in Annalen der Chemie, Volume 616, page 183 (1958) have fungicidal activity.

The parts mentioned in the examples are parts by weight.

example 1

558 parts of mucochloric acid chloride, dissolved in 3,000 parts of dioxane (anhydrous), are slowly mixed with a solution of 960 parts of tryptamine in 7,000 parts of dioxane ^{at 0 to 5 ° C. while stirring.} The mixture is then stirred for 5 hours at room temperature and then poured into water. It is extracted with methylene chloride and the organic phase is shaken with dilute hydrochloric acid. After concentration of the methylene chloride solution to obtain 910 parts (equivalent to 97 $> of theory) of d, ß-dichloro-T ^ -hydroxy-N-ISS-indoyl) -ethyl crotonlactam mp. 167 ⁰ C (decomposition). Analysis: C ₁₄ H ₁₂ O ₂ N ₂ Cl ₂ (311.2)

calculated: C 54.03 % H 3.89 ί> N 9.00 $> Cl 22.79 # found: C 54.12 f » H 3.81 ° ß> N 8.64 $> Cl 22.72 # .

Example 2

If, as described in Example 1, 562.5 parts of mucochloric acid chloride are reacted with 594 parts of cyclohexylamine, 480 parts (corresponds to 64 # of theory) of dUß-dichloro - ^ - hydroxy-N-cyclohexyl-crotone lactam of pp. 156 ^{0 are obtained} C (recrystallized from ether).

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ORIGINAL INSPECTED

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Analysis: G ₁₀ H ₁₃ O ₂ NCl ₂ (250)

Calculated: C 48.0? 6 H 5.2 ^ Cl 28.4 $ N 5.6 56 found: C 48.3 # H 5.0 # Cl 29.0 9ε N 5.2? 6.

Example 3

If, as described in Example 1, 55 parts Mucochlorsäurechlorid with 60 parts of aniline in a way, to obtain 57 parts (equivalent to 79 $> of theory) ^ ß-Mchlor-T ^ hydroxy-N-phenylcrotonlactam from Pp. 134 ⁰ C (recrystallized from ether). λ

Analysis: C ₁₀ H ₇ Cl ₂ O ₂ N (244.1)

Calculated: C 49.20 $ H 2.89 $> N 5.74 1 ° found: C 49.42 i » H 2.98 $ i N 5.45 #.

Example 4

If, as in Example 1 Besca ^ xeuar- Mucochlorsäurechlorid 55 parts with 67 parts of benzylamine in a way, to obtain 58 parts (corresponding to 76 i> of theory) cL, ß-dichloro ^ hydroxy-N-benzylcrotonlactam from Pp. 114 ⁰ C (recrystallized from ether). Analysis: C ₁₁ H ₉ Cl ₂ O ₂ N (258.1)

calculated: C 51.19 1 ° H 3.52 # N 5.43 Ί » found: C 51.31 # H 3.68 $ N 5.31 <fi.

Example 5

If, as indicated in Example 1, 55 parts of mucochloric acid bromide are reacted with 50 parts of benzylamine, 47 parts (corresponds to 76 # of theory) ^, β-dichloro ^ - hydroxy-N-benzyl-crotone lactam of pp. 114 ^{0 are obtained} C (recrystallized from ether).

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Claims (2)

- 8 - υ.-δ. <ο 467 claims 1. Process for the preparation of, ^., Ss-Dihalogen-γ-hydroxy-croton lactams the general formula ι 1 mi I, in which R denotes a hydrogen atom or an aliphatic, cycloaliphatic, araliphatic, aromatic or heterocyclic radical and the individual radicals X can be identical or different and each denote a halogen atom, characterized in that one mucohalogen acid halides of the general formula II, O wherein X has the aforementioned meaning, with ammonia or primary Amines of the general formula R - NH ₂ III, in which R has the aforementioned meaning, at a temperature between -20 and -i 20 ⁰ C converts. 2. djß-Mhalogen-if-hydroxy-crotonlactams of the general formula H _T ^ η R.
1098 Ί5 / 2203 -9- - 9 - O.Z. 25 467 in which R is a hydrogen atom or an aliphatic, cyeLoaliphatic, is araliphatic, aromatic or heterocyclic radical and the individual radicals X are the same or may be different and each denotes a halogen atom. Badische Anilin- & Soda-Fabrik AG 1098-5 / 2203